By reprogramming a 7-year-old girl's own immune cells to attack an aggressive form of childhood leukemia, a pediatric oncologist has achieved a complete response in his patient, who faced grim prospects when she relapsed after conventional treatment. The innovative experimental therapy used bioengineered T cells, custom-designed to multiply rapidly in the patient and then destroy leukemia cells. After the treatment, the child's doctors found that she had no evidence of cancer.

The CTL019 therapy, formerly called CART19, represents a new approach in cancer treatment. T cells are the workhorses of the immune system, recognizing and attacking invading disease cells. However, cancer cells fly under the radar of immune surveillance, evading detection by T cells. Chimeric antigen receptor T cells (CAR T cells) are engineered to specifically target B cells, which become cancerous in certain leukemias, such as ALL and CLL, as well as types of lymphoma, another cancer of the immune cells.

CD19 is a protein found only on the surface of B cells. By creating an antibody that recognizes CD19, and physically connecting that antibody to T cells, the researchers have created a guided missile that locks in on and kills B cells, thereby attacking B-cell leukemia.

This recent report showed that nine of 12 patients with advanced leukemias in the clinical trial, including two children, responded to treatment with CTL019 cells.

One of the nine responding patients is the 7-year-old with acute lymphoblastic leukemia. The treatment was adapted to combat ALL, the most common childhood leukemia, and also the most common childhood cancer. Although physicians can cure about 85% of ALL cases, the remaining 15% of cases stubbornly resist treatment.

By using the CT019 treatment in this pediatric patient, the very activity that destroyed leukemia cells also stimulated a highly activated immune response called cytokine release syndrome. The child became very ill and had to be admitted to the intensive care unit.

Pediatric oncologist Stephan A. Grupp, MD, PhD, of The Children's Hospital of Philadelphia and his team decided to counteract these toxic effects by using two immunomodulating drugs that blunted the overactive immune response and rapidly relieved the child's treatment-related symptoms. These results were effective enough that this approach is now being successfully incorporated into CTL019 treatments for adults as well.

The immunomodulating drugs did not interfere with the CTL019 therapy's anti-leukemia benefits, which persisted for 6 months after the infusion of cell therapy. This persistence is essential, because the engineered T cells remain in the patient's body to protect against a recurrence of the cancer.

“These engineered T cells have proven to be active in B cell leukemia in adults,” said Grupp. “We are excited to see that the CTL019 approach may be effective in untreatable cases of pediatric ALL as well. Our hope is that these results will lead to widely available treatments for high-risk B cell leukemia and lymphoma, and perhaps other cancers in the future.”

Updated results of the clinical trial were presented at the American Society of Hematology (ASH) annual meeting in Atlanta, Georgia, held December 8-11, 2012.